HER2 copy number quantification in primary tumor and cell-free DNA provides additional prognostic information in HER2 positive early breast cancer. (April 2022)

• Record Type: Journal Article
• Authors: Chen, Xiaobin; Lin, Yuxiang; Jiang, Zhengwen; Li, Yan; Zhang, Yihua; Wang, Ying; Yu, Feng; Guo, Wenhui; Chen, Lili; Chen, Minyan; Zhang, Wenzhe; Wang, Chuan; Fu, Fangmeng
• Is Part Of: Breast. Volume 62(2022)Supplement 1
• Page Start: 114
• Page End: 122
• Publication Date: 2022-04
• Subjects: HER2 -- Copy number variation -- Cell-free DNA -- CNVplex -- Prognosis; Breast -- Diseases -- Periodicals; Breast -- Tumors -- Periodicals; Breast -- Periodicals; Electronic journals; Periodicals; 616
• DOI: 10.1016/j.breast.2022.02.002
• Languages: English
• ISSNs: 0960-9776

Abstract

Abstract: Background: The quantitative relationship between HER2 copy number and prognosis in HER2 positive adjuvant setting remain controversial, and few studies have focused on adjuvant setting to illustrate the potential clinical relevance of HER2 in cfDNA. Our study aim to develop a novel method in HER2 quantification and explore the relationship between HER2 copy number in primary tumors or cfDNA and prognosis in HER2 positive early breast cancer. Methods: Two hundred and two patients with early breast cancer were prospectively included in a study where primary tumors, matching non-cancer breast tissue, corresponding plasma, and the plasma from 20 healthy volunteers were collected. Cox proportional hazard analysis was employed to determine the prognostic value of HER2 gene copy number in tissue and cfDNA. Tissue based nomograms and time-dependent decision curve analysis were used to evaluate the practicality of HER2 copy number stratification. Results: HER2 amplification by CNVplex demonstrated a robust concordance with FISH (concordance 89.2%). A three-tiered system of tissue and a two-tiered system of cfDNA classification were shown to be independent prognostic factors. A tissue copy number-based nomogram was fitted and further evaluation revealed a good performance in discrimination (c statistic 0.801) and calibration. Conclusions: We first report CNVplex as a viable alternative for HER2 detection. Quantitative evaluation of HER2 presents tremendous potential for use in risk stratification. We also uncover the potential for using HER2 copy number in cfDNA as a biomarker for prognosis in a HER2 positive adjuvant setting. Highlights: CNVplex was developed to quantify HER2 copy number. HER2 copy number of primary tumor present quantitative relationship with prognosis in HER2 positive early breast cancer. HER2 copy number of cfDNA could function as a biomarker for prognosis.